Comparison of the Medication Effects between Milnacipran and Pregabalin in Fibromyalgia Syndrome Using a Functional MRI: a Follow-up Study

PURPOSE: In this study, the medication effects of Milnacipran and Pregabalin, as well known as fibromyalgia treatment medicine, in fibromyalgia syndrome patients were compared through the change of BOLD signal in pain related functional MRI. MATERIALS AND METHODS: Twenty fibromyalgia syndrome patients were enrolled in this study and they were separated into two groups according to the treatment medicine: 10 Milnacipran (MLN) treatment group and 7 Pregabalin (PGB) treatment group. For accurate diagnosis, all patients underwent several clinical tests. Pre-treated and post-treated fMRI image with block-designed pressure-pain stimulation for each group were obtained to conduct the statistical analysis of paired t-test and two sample t-test. All statistical significant level was less than 0.05. RESULTS: In clinical tests, the clinical scores of the two groups were not significantly different at pre-treatment stage. But, PGB treatment group had lower Widespread Pain Index (WPI) and Brief Fatigue Inventory (BFI) score than those of MLN treatment group at post-treatment stage. In functional image analysis, BOLD signal of PGB treatment group was higher BOLD signal at several regions including anterior cingulate and insula than MLN treatment group at post-treatment stage. Also, paired t-test values of the BOLD signal in MLN group decreased in several regions including insula and thalamus as known as 'pain network'. In contrast, size and number of regions in which the BOLD signal decreased in PGB treatment group were smaller than those of MLN treatment group. CONCLUSION: This study showed that MLN group and PGB group have different medication effects. It is not surprising that MLN and PGB have not the same therapeutic effects since these two drugs have different medicinal mechanisms such as antidepressants and anti-seizure medication, respectively, and different detailed target of fibromyalgia syndrome treatment. Therefore, it is difficult to say which medicine will work better in this study.

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

BACKGROUND/AIMS: A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit. METHODS: Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm). RESULTS: The average charcoal transit was 51.3 +/- 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 +/- 21.9%, 46.9 +/- 9.14% and 8.4 +/- 5.6% of the total small intestine at the concentrations of 10, 30 and 100 microg/kg, respectively. GI transit after administration of TRH (100 microg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 +/- 9.22%; TRH, 73.4 +/- 14.7%; MO, 81.0 +/- 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO. CONCLUSIONS: Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.

Can Platelet-rich Plasma Be Used for Skin Rejuvenation? Evaluation of Effects of Platelet-rich Plasma on Human Dermal Fibroblast

BACKGROUND: Autologous platelet-rich plasma has attracted attention in various medical fields recently, including orthopedic, plastic, and dental surgeries and dermatology for its wound healing ability. Further, it has been used clinically in mesotherapy for skin rejuvenation. OBJECTIVE: In this study, the effects of activated platelet-rich plasma (aPRP) and activated platelet-poor plasma (aPPP) have been investigated on the remodelling of the extracellular matrix, a process that requires activation of dermal fibroblasts, which is essential for rejuvenation of aged skin. METHODS: Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared using a double-spin method and then activated with thrombin and calcium chloride. The proliferative effects of aPRP and aPPP were measured by [3H]thymidine incorporation assay, and their effects on matrix protein synthesis were assessed by quantifying levels of procollagen type I carboxy-terminal peptide (PIP) by enzyme-linked immunosorbent assay (ELISA). The production of collagen and matrix metalloproteinases (MMP) was studied by Western blotting and reverse transcriptase-polymerase chain reaction. RESULTS: Platelet numbers in PRP increased to 9.4-fold over baseline values. aPRP and aPPP both stimulated cell proliferation, with peak proliferation occurring in cells grown in 5% aPRP. Levels of PIP were highest in cells grown in the presence of 5% aPRP. Additionally, aPRP and aPPP increased the expression of type I collagen, MMP-1 protein, and mRNA in human dermal fibroblasts. CONCLUSION: aPRP and aPPP promote tissue remodelling in aged skin and may be used as adjuvant treatment to lasers for skin rejuvenation in cosmetic dermatology.

A New Onset of Systemic Lupus Erythematosus Developed After Bee Venom Therapy

Lupus is a systemic autoimmune disease of an unknown origin, and systemic lupus erythematosus (SLE) can be triggered by numerous stimuli. Bee venom therapy is an alternative therapy that is believed to be effective for various kinds of arthritis. We present here a case of a 49-year-old female who experienced a new onset lupus after undergoing bee venom therapy, and this looked like a case of angioedema. The patient was successfully treated with high dose steroids and antimalarial drugs. We discuss the possibility of bee venom contributing to the development of SLE, and we suggest that such treatment should be avoided in patients with lupus.

Antioxidant Nutrient Intakes and Health Behaviors of Rheumatoid Arthritic Patients / 대한지역사회영양학회지

Previous studies have indicated that incidence of rheumatoid arthritis (RA) is partly related to the damage of antioxidant systems, but etiology of RA is not fully identified. This study was performed to evaluate nutrient intakes including antioxidants, health related behaviors and food habits of RA patients and controls. RA patient group (n = 68) and sex-matched healthy controls (n = 68) were joined in this study. Nutrient intake was estimated using a semiquantitative food frequency questionnaire. As mean age of RA (52.9 +/- 13.8 years) was significantly higher than those of controls (48.7 +/- 5.9 years), data were analyzed by using Student's t-test, adjusted for age. There was no significant difference between two groups in body mass index. Compared with those of controls, frequencies of drinking (p < 0.001) and coffee consumption (p < 0.05) of RA groups were lower. RA groups had lower frequencies of fruit (p < 0.01), vegetable (p < 0.05) and fatty meat (p < 0.05) consumptions and balanced diet (p < 0.01), and higher frequencies of fried dishes (p < 0.01), and salty dishes (p < 0.01), compared to controls. The most nutrient intakes including energy intake of RA were tended to be lower than those of controls. Vitamin A, beta-carotene and vitamin C intakes were significantly lower in RA than controls (p < 0.001). Daily vitamin A, beta-carotene and vitamin C intakes of RA were lower than those of control (vitamin A: RA 360.6 +/- 252.23 microgram RE, control 844.5 +/- 426.2 microgram RE, p < 0.001; beta-carotene: RA 1450.9 +/- 1019.0 microgram, control 3968.8 +/- 2248.21 microgram, p < 0.001; vitamin C; RA 40.6 +/- 21.48 mg,control 84.7 +/- 40.29, p < 0.001) These results suggest sufficient consumption of antioxidant nutrients may prevent and improve RA status.

Autologous Stem Cell Transplantation for the Treatment of Neuroblastoma in Korea

Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.

Spinal and Supraspinal Changes in Vitamin D3 Up-regulated Protein 1 (VDUP1) Gene Expression after Spinal Cord Injury / 대한마취과학회지

BACKGROUND: Vitamin D3 up-regulated protein 1 (VDUP1) gene is known to be a novel member of the early response genes and an oxidative stress mediator. This study was designed to elucidate VDUP1 expression and its involvement in central sensitization after spinal cord injury (SCI). METHODS: Contusion injury was produced at spinal segment T10 (20 mm drop, 10 g rod) in adult male Sprague-Dawley rats (250 300 g). Withdrawal responses were measured using von Frey filaments and acetone on the 1st, 3rd and 7th days after SCI. The expressions of VDUP1 gene in the brain and in the cervical and lumbar spine were examined by immunohistochemistry on the 1st, 3rd and 7th day after SCI. RESULTS: VDUP1 gene was detected in a few oligodendrocytes in the spinal cord and in the brain of control rats. VDUP1 gene expression increased in most of the neurons and ependymal cells in the central canal of the injured (lumbar) spinal cord 1 day after SCI. This expression gradually decreased in majority of cells from day 1 to day 7 after SCI. VDUP1 gene expression was also observed to be increased 1 day after SCI, and gradually to decrease from 1 day to 7 days after SCI. The neurons in the intact (cervical) spinal cord VDUP1 gene expression increases maximally 3 days after SCI in the cerebral cortex and the thalamus. Neuropathic pain behavior was triggered by the plantar surface of the fore foot after SCI. CONCLUSIONS: These results show that the VDUP1 gene may be an early modulator of transneuronal stress response after SCI, and to be related to the central sensitization of neuropathic pain behavior after SCI.

Changes in Myogenic Tone in Spontaneously Hypertensive Rat: Role of RhoA and Protein Kinase C

BACKGROUND AND OBJECTIVES: The myogenic response was originally described as a contraction of a blood vessel that occurred following an increase in intravascular distending pressure. Conversely, a reduction in intravascular pressure produces myogenic vascular relaxation. Recent attention has focused on the potential role of this myogenic mechanism in the control of tone in the resistance vasculature, and in particular on how this mechanism may contribute to the increased vascular resistance seen in hypertension. Therefore, in the present study, we investigated the role of myogenic tone in the generation and/or maintenance of hypertension. MATERICAL AND METHODS: Myogenic tone was developed by stretching of the basilar arteries of WKY (istar Kyoto rat) and SHR (spontaneously hypertensive rats). Contractile responses, PKC (protein kinase C) immunoblots and translocation of PKC and RhoA were measured. In the presence of extracellular Ca2+ the stretching of the resting vessel evoked a myogenic contraction in the basilar arteries of SHR and WKY. Myogenic tone was significantly greater in SHR than in WKY. However, in the absence of extracellular Ca2+, stretching evoked a myogenic contraction in SHR, but not in WKY. The stretch-induced myogenic tone was inhibited by nifedipine. The effect of nifedipine was similar in both SHR and WKY rats. H-7, calphostin C and Y-27632, also inhibited stretch-induced myogenic tone in both SHR and WKY. The inhibitory effects of these drugs were greater in SHR than in WKY. Immunoblotting showed rho A and PKC alpha were translocated from the cytosol to the cell membrane with stretching in both SHR and WKY. PKC beta, however, was translocated to the cell membrane with stretching in SHR, but not in WKY. CONCLUSION: These results suggest that stretch-induced myogenic tone is significantly greater in SHR than in WKY. Furthermore, the increase in amount and/or activity of PKC beta and ROK (rhoA-associated kinase) may be a key mechanism accounting for the enhanced myogenic tone in SHR.

Mechanism of L-NAME-resistant endothelium-dependent relaxation induced by acetylcholine in rabbit renal artery

In the rabbit renal artery, acetylcholine (ACh, 1 nM ~ 10 micrometer) induced endothelium-dependent relaxation of arterial rings precontracted with norepinephrine (NE, 1 micrometer) in a dose-dependent manner. NG-nitro-L-arginine (L-NAME, 0.1 mM), an inhibitor of NO synthase, or ODQ (1 micrometer), a soluble guanylate cyclase inhibitor, partially inhibited the ACh-induced endothelium-dependent relaxation. The ACh-induced relaxation was abolished in the presence of 25 mM KCl and L-NAME. The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10 micrometer), miconazole (10 micrometer), or 17-octadecynoic acid (17-ODYA, 10 micrometer), failed to inhibit the ACh-induced relaxation in the presence of L-NAME. 11,12-epoxyeicosatrienoic acid (11,12-EET, 10 micrometer) had no relaxant effect. The ACh-induced relaxation observed in the presence of L-NAME was significantly reduced by a combination of iberiotoxin (0.3 micrometer) and apamin (1 micrometer), and almost completely blocked by 4-aminopyridine (5 mM). The ACh-induced relaxation was antagonized by P2Y receptor antagonist, cibacron blue (10 and 100 micrometer), in a dose-dependent manner. Furthermore, 2-methylthio-ATP (2MeSATP), a potent P2Y agonist, induced the endothelium-dependent relaxation, and this relaxation was markedly reduced by either the combination of iberiotoxin and apamin or by cibacron blue. In conclusion, in renal arteries isolated from rabbit, ACh produced non-NO relaxation that is mediated by an EDHF. The results also suggest that ACh may activate the release of ATP from endothelial cells, which in turn activates P2Y receptor on the endothelial cells. Activation of endothelial P2Y receptors induces a release of EDHF resulting in a vasorelaxation via a mechanism that involves activation of both the voltage-gated K+ channels and the Ca2+-activated K+ channels. The results further suggest that EDHF does not appear to be a cytochrome P450 metabolite.

The Effect of Benzathine Penicillin-induced Focal Interictal Epileptiform Discharges on the Expression Patterns of c-JUN Protein in the Rat Brain

BACKGROUND: Immediate early gene (IEG) is supposed to be linked in the continuous seizure induced long-term changes of specific neurons. We tried to investigate the effects of focal interictal epileptiform discharges on the c-JUN expression in the rat brain which is not clearly understood. METHODS:Epidural electrodes were placed on a male Sprague-Dawley weighing 150~230 g and benzathine penicillin (Pc) was applied cortically. After focal interictal epileptiform discharges were successfully identified, EEG was recorded regularly. Cardiac perfusion and extraction of the brain was done at 2, 4, 24 hours and 1 week after the Pc application. Sixteen rats were evenly distributed into 4 groups. Immunocytochemical staining with specific antisera (Santa Cruz) was performed. RESULTS: The epileptiform discharges were induced within an hour after topical Pc applications. At 2 hours after Pc application, c-JUN was moderately expressed in the dentate gyrus (DG) and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. At 4 hours, c-JUN was minimally expressed in DG and other regions. Whereas, at 24 hours, c-JUN was maximally expressed in the DG and also in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. One week after Pc application, c-JUN was moderately expressed in the DG and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, and neocortex. CONCLUSIONS: This data showed that even focal interictal epileptic activity can induce IEG encoded c-JUN protein in the specific distant brain regions of a rat until a late period and the expression pattern showed a synchronous and bimodal pattern.

Pharmacotherapy of Eating Disorders / 대한정신약물학회지

One of the true success stories in clinical neurosciences over the last 30 or so years has been the development of effective drug therapies of several psychiatric disorders including schizophrenia. It is true that the effects of drug are not disease-specific. However, it if logical to find medications that will be effective in eating disorders. In spite of many limitations, some tentative conclusions regarding the role of medications in the treatment of eating disorders can now be drawn. These conclusions as a whole revealed the following ; 1) There were no clear difference in efficacy among the various drugs used. 2) Short-term abstinence rates are about 30%, and overall reductions in bulimic behavior are about 70%. 3) A significant relapse rate(30-45%) is observed if patients are followed for 4-6 months. 4) There are few predictors of who will respond to these medications. 5) Dropout rates tend to be high, in part because of side effects and in part because of some patients' attitudes toward medication use. 6) The doses used in these treatment studies have generally been similar to those employed in the treatment of depression, and with a single exception which the high-dose regimen (60 mg of fluoxetine) was clearly superior to the loll dose (20 mg of fluoxetine). However, Wakeling(1995) suggested that the pharmacotherapy for eating disorders clearly had some limited beneficial effects, at least in the short term and that many unanswered questions remained related to the acceptability of this form of treatment, the unwanted effects of drugs and the longer-term efficacy. He also insisted that at the present level of knowledge, pharmacotherapy should not be used as a sole treatment approach but only within an overall treatment programme. In clinical practice, pharmacotherapy is frequently used in the treatment of eating disorders in combination with various psychotherapuetic approaches. Therefore, the clinicians, who engage in the treatment of patients with eating disorders, should be able to identify the patients for whom drug therapy is desirable and be accustomed to the differences with the pharmacotherapy of other psychiatric patients. The author will review the results of previous studies on pharmacotherapy for eating disorders and demonstrate several important issues in the practice of pharmacotherapy for the patients with eating disorders.

Nutritional Assessment and Dietary Management during Anti-Cancer Chemotherapy in Pediatric Oncology Patients / 대한소아소화기영양학회지

PURPOSE: We assessed the nutritional status and the alterations of oral diets during anti-cancer chemotherapy in pediatric oncology patients. METHODS: Twenty children with malignancy were evaluated from day 0 until day 21 of post-chemotherapy. Nutritional status was assessed by body weight and biochemical parameters. The amount and calories of oral diets were assessed and food preference before and during chemotherapy were analysed by questionnelle. RESULTS: 1) The underlying diseases of 20 patients were 11 acute lymphoblastic lekemia, 2 non-Hodgkin's lymphoma, 2 Langerhans cell histiocytosis, 2 Wilm's tumor, 2 brain tumor, 1 rhabdomyosarcoma. 2) There were weight loss during chemotherapy in 8 patients (40.0%), weigt gain in 5 patients (25.0%), and no significant changes in 7 patients (35.0%). 3) Biochemical parameters showed no significant interval changes during chemotherapy except elevation of serum ALT level. 4) The daily caloric intakes of oral diets during chemotherapy were 310~600 Kcal which was much lower than average of daily recommended calory for Korean children. 5) The most favorate food was altered by chemotherapy, from meats to carbonated beverages and unfavorate food was not altered as vegetables. CONCLUSION: The periodic assessment of nutritional status and dietary supplements according to preferred foods of patients will be required for the optimal nutrition care in cancer patients.

Study on the Mechanism of Hypoxic Induced Vasodilatation and Vasoconstriction

BACKGROUND: Although hypoxic pulmonary vasoconstriction (HPC) and hypoxic coronary vasodilatation (HCD) have been recognized by many researchers, the precise mechanism remains unknown. As isolated arteries will constrict or relax in vitro in response to hypoxia, the oxygen sensor/transduction mechanism must reside in the arterial smooth muscle, the endothelium, or both. Unfortunately, much of the current evidence is conflicting, especially concerning to the dependency of HPC and HCD on the endothelium and the role of the K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPC and HCD on the endothelium and the role of the K+ channel on HPC and HCD. METHODS: HPC was investigated in isolated main pulmonary arteries precontracted with norepinephrine (NE). HCD was investigated in isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 +5% CO2, which was maintained for 15 - 25 min. RESULTS: 1)Hypoxia elicited a vasoconstriction in NE-precontracted pulmonary arteries with endothelium, but a vasodilatation in PGF 2 alpha-precontracted coronary arteries with and without endothelium. There was no difference between the amplitude of the HPC and HCD induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on subsequent response to hypoxia. 2)Inhibition of NO synthesis by the treatment with Nw-nitro-L-arginine reduced HPC in pulmonary arteries, but inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HPC and HCD, respectively. 3)Blockades of the TEA-sensitive K+ channel abolished HPC and HCD. 4)Apamin, a small conductance Ca2+/-activated K+ (KCa) channel blocker, and iberiotoxin, a large conductance KCa channel blocker, had no effect on the HCD. 5)Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, reduced HCD. 6)Cromakalim, an K(ATP) channel opener, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia and glibenclamide reduced both hypoxia- and cromakalim-induced vasodilations. 7)Verapamil, a Ca2+ entry blocker, caffeine, a Ca2+ emptying drug; and ryanodine, an inhibitor of Ca2+ release from SR, reduced HPC, respectively. CONCLUSION: HPC is dependent on the endothelium and is considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation while HCD is independent of the endothelium and is considered to be induced by activation of the K(ATP) channel.

Action mechanisms of NANC neurotransmitters in smooth muscle of guinea pig ileum

The relaxation induced by stimulation of the inhibitory non-adrenergic, non-cholinergic (iNANC) nerve is mediated by the release of iNANC neurotransmitters such as nitric oxide (NO), vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP). The mechanisms of NO, VIP or ATP-induced relaxation have been partly determined in previous studies, but the detailed mechanism remains unknown. We tried to identify the nature of iNANC neurotransmitters in the smooth muscle of guinea pig ileum and to determine the mechanism of the inhibitory effect of nitric oxide. We measured the effect of NO-donors, VIP and ATP on the intracellular Ca2+ concentration((Ca2+)i), by means of a fluorescence dye (fura 2) and tension simultaneously in the isolated guinea pig ileal smooth muscle. Following are the results obtained. 1. Sodium nitropnisside (SNP: 10(-5) M) or S-nitro-N-acetyl-penicillamine (SNAP: 10(-5) M) decreased resting (Ca2+)i and tension of muscle. SNP or SNAP also inhibited rhythmic oscillation of (Ca2+)i and tension. In 40mM K+ solution or carbachol (CCh:10(-6) M)-induced precontracted muscle, SNP decreased muscle tension. VIP did not change (Ca2+)i and tension in the resting or precontracted muscle, but ATP increased resting (Ca2+)i and tension in the resting muscle. 2. 1H-(1,2,4)oxadiazol(4,3-a)quinoxalin-1-one (ODQ:1 muM), a specific inhibitor of soluble guanylate cyclase, limited the inhibitory effect of SNP. 3. Glibenclamide (10 muM), a blocker of KATP channel, and 4-aminopyridine (4-AP:5 mM), a blocker of delayed rectifier K channel, apamin (0.1 muM), a blocker of small conductance KCa. channel had no effect on the inhibitory effect of SNP. Iberiotoxin (0.1 muM), a blocker of large conductance KCa channel, significantly increased the resting (Ca2+)i, and tension, and limited the inhibitory effect of SNP. 4. Nifedipine (1 muM) or elimination of external Ca2+ decreased not only resting (Ca2+)i and tension but also oscillation of (Ca2+)i and tension. Ryanodine (5 muM) and cyclopiazonic acid (10 muM) decreased oscillation of (Ca2+)i and tension. 5. SNP decreased Ca2+ sensitivity of contractile protein. In conclusion, these results suggest that 1) NO is an inhibitory neurotransmitter in the guinea pig ileum, 2) the inhibitory effect of SNP on the (Ca2+)i and tension of the muscle is due to a decrease in (Ca2+)i by activation of the large conductance KCa channel and a decrease in the sensitivity of contractile elements to Ca2+ through activation of G-kinase.

Prophylactic Treatment of Anemia of Prematurity with Recombinant Human Erythropoietin and High Doses of Iron

PURPOSE: We conducted randomized study to determine whether high doses (6mg/kg/ day) of iron would exert a more supplemental effect than low doses (3mg/kg/day), and which regimen of recombinant human erythropoietin (rHuEPO) and iron would be more beneficial in the prophylactic treatment of anemia of prematurity. METHODS: We randomly assigned 38 sick premature infants who were more likely than symptom-free premature infants requiring erythrocyte transfusions for infants with anemia of prematurity to receive rHuEPO, 100unit/kg, tiw, subcutaneously, plus iron, 3mg/kg/day, po, daily from the second day of life (group 1), 100unit/kg and 6mg/kg/ day (group 2), 200unit/kg and 3mg/kg/day (group 3), and 200unit/kg and 6mg/kg/day (group 4), respectively. RESULTS: There were no significant differences of hemoglobin levels and iron balances during treatment among all 4 groups. The rates of increase in reticulocyte counts were greater in group 4 and group 2 compared with group 3 and group 1, respectively, though these rates were statistically not significant. The blood volume differences (volume of phlebotomies-volume of transfusions) during treatment were higher in group 4 compared with group 1 (p<0.05). CONCLUSIONS: High doses of iron may be more effective in rapidly increasing reticulocyte counts, and 200unit/kg, tiw of rHuEPO plus 6mg/kg/day of iron is more beneficial in reducing the need for blood transfusions than any other regimen. Therefore the prophylactic treatment of anemia of prematurity and acute blood loss from frequent blood sampling in risky premature infants with rHuEPO, 200unit/kg, tiw, subcutaneously, plus iron 6mg/kg/day, po, daily from the second day of life is effective in reducing the number of blood transfusions. Additional controlled trials utilizing high doses of iron with rHuEPO and larger numbers of patients are justified.

A Study on Blood Lead Levels in Pediatric Inpatients

Lead is one of the most widespread environmental toxins and its poisoning in children was considered a rarity, usually resulting from unique circumstances such as inappropriate use of leadbased body cosmetics or direct administration of lead-containing folk medicines. The increasing concern about children with lower levels of lead exposure has developed, but there are no data regarding the mean blood lead levels and the incidence of symptomatic or asymptomatic lead poisoning in Korean children. We analyzed the zinc protoporphyrine (ZPP) values and blood lead concentrations in 163 pediatric inpatients for a prospective study of lead exposure. The blood lead concentrations in all 163 children were 15~54 g/dl, of whom 111 children (68.1%) were 25~54 g/dl which needs decision to chelate based on the EDTA provocation test. Among 111 children whose blood lead concentrations are 25~54 g/dl, 59 children(53.2%) were between 7 months and 3 years of age, which revealed no significant higher incidence of lead exposure than any other age group. The ZPP values in 126 children (77.3%) were above 35 g/dl. The mean blood lead concentration and ZPP values are 27.8 g/dl and 48.8 g/dl, respectively. We conclude that there are many asymptomatic children with increased absorption of lead in the urban area of Korea, and we need further studies regarding lead poisoning. It is important that there must be a national counterplan and that pediatricians continue to pay attention to lead posioning in children.

Effect of Teramethylammonium on the Release of Endothelium-Derived Relaxing Factor in Rabbit Thoracic Aorta

Teramethylammonium(TMA) in one of the synthetic compounds of nicotine that act at ganglionic site. The major action of TMA consists of initial stimulation followed by a more persistent depression of all autonomic ganglia by binding to a cholinergic receptor. It is well believed that the level of membrane potential in arterial smooth muscle is an important regulator of tension development. Depolarization and hyperpolarization by only few millivolts results in significant changes in tension. In general, the agents of vascular smooth muscle induce vascular relaxaion. The present study was undertaken to elucidate the effect of TMA on vascular contractility in the isolated rabbit thoracic aorta with or without endothelial cell, and mechanisms involved in the change of vascular contractility by TMA. The results obtained are summarized as follows ; 1) In the presence of endothelial cell, TMA induced a relaxtion of the aorta precontracted with norepinephrine but induced a contraction in the aorta without endothelial cells, indicating that in the rabbit aorta, relaxations produced by TMA were the endothelium-dependent. 2) The addition of inhibitor such as methylene blue, hemoglobin, hydroquinone and p-bromophenacyl bromide during the TMA-induced relaxation reversed the contractile tension to a level similar to or higher than that before the addition of TMA in rabbit thoracic aorta.This relaxation effect of TMA suggest that the TMA-inducdd relaxation in rabbit aorta is due to the release of endotheline derived relaxing factor(EDRF). 3) Relaxation induced by TMA was antagonized by atropine and thus the TMA does seem to act on the muscarinic receptors. 4) TMA reduced the norepinephrine-induced Ca++ influx into rabbit smooth muscle membrane. From the above results, it may be concluded that TMA-induced vacular relaxation in rabbit aorta is due to the release of EDRF. Mechanism involved in the relaxation induced by TMA may be the stimulation of soluble guanylate cyclase and increased tissue cGMP concentrations.

Relationship Between Dorsal Horn Cell Activity and Electrical Stimulation of Peripheral Nerve with Special Reference of Stimulatory Parameters

Transcutaneous electrical nerve stimulation (TENS), acupuncture-needling, and electroacu! Puncture are useful non-ablative methods in medical practice for relief of acute and chronic r pain These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. The present study was performed to evaluate the analgesic effects of peripheral nerve stimulation with different stimulatory parameters in decerebrated cats and spinalized cats. And we studied the effects of naloxone, a specific opiate antagonist, on analgesia produced by 50 Hz, C intensity conditioning stimulation. The electrical response of.spinal neurons was elicited either by electrical stimulation of the ipsilateral common peroneal nerve or tibial nerve, and then the single unit activity of the dorsal horn cell was recorded with a carbon filament-filled glass microelectrode at the lumbosacral spinal cord. The conditioning stimuli which provoke the pain inhibitory mechanism were applied to the cornmon peroneal nerve or tibial nerve with a relatively high frequency (25, 50, 200Hz) for 15, 30, and 60 seconds at suprathreshold intensity for A delta or C fiber. The results of the experiment are summarized as follows: 1. Peripheral conditioning stimulation at C strength showed larger analgesic effects than those produced by stimulation at A delta strength. And analgesic effects produced by conditioning stimulation for 30sec were greater than those produced by stimulation for 15sec, but showed no statistically significant difference from those produced by stimulation for 60 sec. 2. Analgesic effects produced by 50Hz conditioning stimulation were greater than thoseproduced by 25Hz stimulation. But 200Hz stimulation showed a lesser analgesic effect than 50 or 25Hz conditioning stimulation. 3. The analgesic effect produced by 50Hz conditioning stimulation was only slightly affected by naloxone, a specific opiate antagonist, indicating that involvement of an endogenous opiate system was minimal. 4. The analgesic effect produced by conditioning stimulation in decerebrated cats was nearly the same as in spinal cats suggesting that the neural circuitry responsible for the analgesic action seems to reside mostly within the spinal cord. From the above results, it is concluded that 1) frequency of stimulation is important for an efficient analgesia, i.e., stimulation with excessively high frequency decreases the analgesic effect, 2) the analgesic effect produced by high frequency conditioning stimulation may be minimally mediated by an endogenous opiate system, and 3) the site of analgesic action resides mainly in the spinal cord.